Streptococci are a group of bacteria with the capacity to grow in chains. Many varieties are part of the normal bacterial flora in humans and are not especially harmful. However, a particular group of streptococcal bacteria, called group A and represented by Streptococcus pyogenes, is a human pathogen. Briefly, group A streptococci cause a variety of human illnesses, ranging from uncomplicated pharyngitis and pyoderma to life-threatening infections associated with toxic shock syndrome, deep tissue invasion and sepsis. In some individuals, untreated streptococcal pharyngitis may be followed by acute rheumatic fever. In recent years there has been a dramatic increase in the incidence of severe streptococcal infections (Davies et al., “Invasive group A streptococcal infections in Ontario, Canada. Ontario group A Streptococcal study group,” N. Engl. J. Med. 335:547-554, 1996) and in the incidence of rheumatic fever (Veasey et al., “Resurgence of acute rheumatic fever in the intermountain region of the United States,” N. Eng. J. Med. 316:421-427, 1987).
Although streptococcal infections can be generally treated with antibiotics, in at least 4% of cases the infection leads to acute rheumatic fever. This disease is particularly prevalent in developing countries such as India, where millions of school-age children are affected.
The present invention provides new Group A streptococcal vaccines with enhanced immunogenicity, and further, provides other related advantages.